| Chelation therapy | |
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Two molecules of deferasirox, an orally administered chelator, binding iron. Deferasirox is used in the treatment of transfusional iron overload in people with thalassemia.
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Chelation therapy is a medical procedure that involves the administration of chelating agents to remove heavy metals from the body. Chelation therapy has a long history of use in clinical toxicology and remains in use for some very specific medical treatments, although it is administered under very careful medical supervision due to various inherent risks.
Chelation therapy must be administered with care as it has a number of possible side effects, including death. In response to increasing use of chelation therapy as alternative medicine and in circumstances in which the therapy should not be used in conventional medicine, various health organizations have confirmed that medical evidence does not support the effectiveness of chelation therapy for any purpose other than the treatment of heavy metal poisoning. Over-the-counter chelation products are not approved for sale in the United States.
Medical uses
Chelation therapy is the preferred medical treatment for metal poisoning, including acute mercury, iron (including in cases of sickle-cell disease and thalassemia), arsenic, lead, uranium, plutonium and other forms of toxic metal poisoning. The chelating agent may be administered intravenously, intramuscularly, or orally, depending on the agent and the type of poisoning.
Chelating agents
There
are a variety of common chelating agents with differing affinities for
different metals, physical characteristics, and biological mechanism of action. For the most common forms of heavy metal intoxication – lead, arsenic, or mercury – a number of chelating agents are available. Dimercaptosuccinic acid (DMSA) has been recommended for the treatment of lead poisoning in children by poison control centers around the world. Other chelating agents, such as 2,3-dimercaptopropanesulfonic acid (DMPS) and alpha lipoic acid (ALA), are used in conventional and alternative medicine. Some common chelating agents are ethylenediaminetetraacetic acid (EDTA), 2,3-dimercaptopropanesulfonic acid (DMPS), and thiamine tetrahydrofurfuryl disulfide
(TTFD). Calcium-disodium EDTA and DMSA are only approved for the
removal of lead by the Food and Drug Administration while DMPS and TTFD
are not approved by the FDA. These drugs bind to heavy metals in the
body and prevent them from binding to other agents. They are then
excreted from the body. The chelating process also removes vital
nutrients such as vitamins C and E, therefore these must be
supplemented.
The German Environmental Agency (Umweltbundesamt) listed DMSA and
DMPS as the two most useful and safe chelating agents available.
| Chelator | Used in |
|---|---|
| Dimercaprol |
|
| Dimercaptosuccinic acid | |
| Dimercapto-propane sulfonate (DMPS) |
|
| Penicillamine | Mainly in:
Occasionally adjunctive therapy in:
|
| Ethylenediamine tetraacetic acid | |
| Deferoxamine and Deferasirox |
|
Side effects
When used properly in response to a diagnosis of harm from metal toxicity, side effects of chelation therapy include dehydration, low blood calcium, harm to kidneys, increased enzymes as would be detected in liver function tests, allergic reactions, and lowered levels of dietary elements. When administered inappropriately, there are the additional risks of hypocalcaemia (low calcium levels), neurodevelopmental disorders, and death.
History
Chelation therapy can be traced back to the early 1930s, when Ferdinand Munz, a German chemist working for I.G. Farben, first synthesized ethylenediaminetetraacetic acid (EDTA). Munz was looking for a replacement for citric acid as a water softener. Chelation therapy itself began during World War II when chemists at the University of Oxford searched for an antidote for lewisite, an arsenic-based chemical weapon. The chemists learned that EDTA was particularly effective in treating lead poisoning.
Following World War II, chelation therapy was used to treat
workers who had painted United States naval vessels with lead-based
paints.
In the 1950s, Norman Clarke, Sr. was treating workers at a battery
factory for lead poisoning when he noticed that some of his patients had
improved angina pectoris following chelation therapy.
Clarke subsequently administered chelation therapy to patients with
angina pectoris and other occlusive vascular disease and published his
findings in The American Journal of the Medical Sciences in December 1956. He hypothesized that "EDTA could dissolve disease-causing plaques in the coronary systems of human beings." In a series of 283 patients treated by Clarke et al. From 1956-1960, 87% showed improvement in their symptomatology.
Other early medical investigators made similar observations of EDTA's
role in the treatment of cardiovascular disease (Bechtel, 1956; Bessman,
1957; Perry, 1961; Szekely, 1963; Wenig, 1958: and Wilder, 1962).
In 1973, a group of practicing physicians created the Academy of Medical Preventics (now the American College for Advancement in Medicine). The academy trains and certifies physicians in the safe administration of chelation therapy.
Members of the academy continued to use EDTA therapy for the treatment
of vascular disease and developed safer administration protocols.
In the 1960s, BAL was modified into DMSA, a related dithiol with far fewer side effects.
DMSA quickly replaced both BAL and EDTA as the primary treatment for
lead, arsenic and mercury poisoning in the United States. Esters of DMSA
have been developed which are reportedly more effective; for example,
the monoisoamyl ester (MiADMSA) is reportedly more effective than DMSA
at clearing mercury and cadmium. Research in the former Soviet Union led to the introduction of DMPS, another dithiol, as a mercury-chelating agent. The Soviets also introduced ALA, which is transformed by the body into the dithiol dihydrolipoic acid,
a mercury- and arsenic-chelating agent. DMPS has experimental status in
the United States, while ALA is a common nutritional supplement.
Since the 1970s, iron chelation therapy has been used as an alternative to regular phlebotomy to treat excess iron stores in people with haemochromatosis.
Other chelating agents have been discovered. They all function by
making several chemical bonds with metal ions, thus rendering them much
less chemically reactive. The resulting complex is water-soluble,
allowing it to enter the bloodstream and be excreted harmlessly.
Calcium-disodium EDTA chelation has been studied by the U.S. National Center for Complementary and Alternative Medicine for treating coronary disease. In 1998, the U.S. Federal Trade Commission (FTC) pursued the American College for Advancement in Medicine
(ACAM), an organization that promotes "complementary, alternative and
integrative medicine" over the claims made regarding the treatment of atherosclerosis
in advertisements for EDTA chelation therapy. The FTC concluded that
there was a lack of scientific studies to support these claims and that
the statements by the ACAM were false.
In 1999, the ACAM agreed to stop presenting chelation therapy as
effective in treating heart disease, avoiding legal proceedings.
In 2010 the U.S. Food and Drug Administration (FDA) warned companies
who sold over-the-counter (OTC) chelation products and stated that such
"products are unapproved drugs and devices and that it is a violation of
federal law to make unproven claims about these products. There are no
FDA-approved OTC chelation products."
Society and culture
In 1998, the U.S. Federal Trade Commission
(FTC) charged that the web site of the American College for Advancement
in Medicine (ACAM) and a brochure they published had made false or
unsubstantiated claims. In December 1998, the FTC announced that it had
secured a consent agreement barring ACAM from making unsubstantiated
advertising claims that chelation therapy is effective against
atherosclerosis or any other disease of the circulatory system.
In August 2005, doctor error led to the death of a five-year-old autistic boy who was undergoing chelation therapy. Others, including a three-year-old nonautistic girl and a nonautistic adult, have died while undergoing chelation therapy. These deaths were due to cardiac arrest caused by hypocalcemia
during chelation therapy. In two of the cases hypocalcemia appears to
have been caused by the administration of Na2EDTA (disodium EDTA) and in
the third case the type of EDTA was unknown. Only the 3-year-old girl had found to have an elevated blood lead level and resulting low iron levels and anemia, which is the conventional medical cause for administration of chelation therapy. According to protocol, EDTA should not be used in the treatment of children. More than 30 deaths have been recorded in association with IV-administered disodium EDTA since the 1970s.
Use in alternative medicine
In alternative medicine, some practitioners claim chelation therapy can treat a variety of ailments, including heart disease and autism. The use of chelation therapy by alternative medicine practitioners for behavioral and other disorders is considered pseudoscientific; there is no proof that it is effective.
In addition to being ineffective, chelation therapy prior to heavy
metal testing can artificially raise urinary heavy metal concentrations
(“provoked” urine testing) and lead to inappropriate and unnecessary
treatment. The American College of Medical Toxicology and the American Academy of Clinical Toxicology
warn the public that chelating drugs used in chelation therapy may have
serious side effects, including liver and kidney damage, blood pressure
changes, allergies and in some cases even death of the patient.
Cancer
The American Cancer Society
says of chelation therapy: "Available scientific evidence does not
support claims that it is effective for treating other conditions such
as cancer. Chelation therapy can be toxic and has the potential to cause
kidney damage, irregular heartbeat, and even death."
Cardiovascular disease
The U.S. National Center for Complementary and Alternative Medicine (NCCAM) conducted a trial on the chelation therapy's safety and efficacy for patients with coronary artery disease. NCCAM Director Stephen E. Straus
cited the "widespread use of chelation therapy in lieu of established
therapies, the lack of adequate prior research to verify its safety and
effectiveness, and the overall impact of coronary artery disease" as
factors motivating the trial.
The study has been criticized by some who said it was unethical,
unnecessary and dangerous, and that multiple studies conducted in prior
to it demonstrated that the treatment provides no benefit.
According to the findings of a 1997 systematic review, EDTA chelation therapy is not effective as a treatment for coronary artery disease and this use is not approved in the United States by the US Food and Drug Administration (FDA). Several possible mechanisms for its efficacy have been proposed, though none have been scientifically validated.
The American Heart Association
stated in 1997 that there is "no scientific evidence to demonstrate any
benefit from this form of therapy." The United States Food and Drug
Administration (FDA), the National Institutes of Health (NIH) and the American College of Cardiology
"all agree with the American Heart Association" that "there have been
no adequate, controlled, published scientific studies using currently
approved scientific methodology to support this therapy for
cardiovascular disease."
They speculate that any improvement among heart patients undergoing
chelation therapy can be attributed to the placebo effect and generally
recommended lifestyle changes such as "quitting smoking, losing weight,
eating more fruits and vegetables, avoiding foods high in saturated fats
and exercising regularly." They also are concerned that patients could
put off proven treatments for heart disease like drugs or surgery.
A systematic review published in 2005 found that controlled scientific studies did not support chelation therapy for heart disease.
It found that very small trials and uncontrolled descriptive studies
have reported benefits while larger controlled studies have found
results no better than placebo.
In 2009, the Montana Board of Medical Examiners issued a position
paper concluding that "chelation therapy has no proven efficacy in the
treatment of cardiovascular disease, and in some patients could be
injurious."
The final results of TACT were published in November 2012. The
authors concluded that disodium EDTA chelation "modestly" reduced the
risk of adverse cardiovascular outcomes among stable patients with a
history of myocardial infarction. The study also showed a "marked" reduction in cardiovascular events in diabetic patients treated with EDTA chelation. An editorial published in the Journal of the American Medical Association
said that "the study findings may provide novel hypotheses that merit
further evaluation to help understand the pathophysiology of secondary
prevention of vascular disease."
Critics of the study characterized the study as showing no support for
the use of chelation therapy in coronary heart disease, particularly the
claims to reduce the need for coronary artery bypass grafting (CABG, pronounced "cabbage").
The US National Center for Complementary and Alternative Medicine began the Trial to Assess Chelation Therapy (TACT) in 2003. Patient enrollment was to be completed around July 2009 with final completion around July 2010, but enrollment in the trial was voluntarily suspended by organizers in September 2008 after the Office for Human Research Protections began investigating complaints such as inadequate informed consent.
Additionally, the trial was criticized for lacking prior Phase I and II
studies, and critics summarized previous controlled trials as having
"found no evidence that chelation is superior to placebo for treatment
of CAD or PVD." The same critics argued that methodological flaws and lack of prior probability made the trial "unethical, dangerous, pointless, and wasteful." The American College of Cardiology supported the trial and research to explore whether chelation therapy was effective in treating heart disease.
Evidence of insurance fraud and other felony convictions among
(chelation proponent) investigators further undermined the credibility
of the trial.
Autism
Quackwatch
says that autism is one of the conditions for which chelation therapy
has been falsely promoted as effective, and practitioners falsify
diagnoses of metal poisoning to "trick" parents into having their
children undergo the risky process. As of 2008, up to 7% of children worldwide with autism had been subjected to chelation therapy. The death of two children in 2005 was caused by the administration of chelation treatments, according to the American Center for Disease Control. One of them was autistic. Parents either have a doctor use a treatment for lead poisoning, or buy unregulated supplements, in particular DMSA and lipoic acid. Aspies For Freedom, an autism rights organization, considers this use of chelation therapy unethical and potentially dangerous.
There is little to no credible scientific research that supports the
use of chelation therapy for the effective treatment of autism.
